Direct cortical feedforward and feedback pathways differentially shape visual responses and selectively engage looped circuits

Nearly every computational account of hierarchical cortex rests on assumptions about the influence of direct cortico-cortical inputs and which neurons they act upon. Yet, disentangling their direct functional contributions from indirect, multisynaptic influences remains difficult. We examined how feedforward (FF) and feedback (FB) pathways between mouse primary visual cortex (V1) and posteromedial cortex (PM) modulate visual responses, combining retrograde labelling, multi-area two-photon imaging and optogenetic perturbations. High or low activity in either pathway was associated with both excitation and inhibition of neurons in the targeted areas. FF activity was associated with stronger additive changes, while FB activity was related to stronger multiplicative modulations and improvements in visual decoding. Optogenetic manipulations causally confirmed these asymmetries. Both pathways preferentially modulated reciprocating "looped" neurons, with FF exciting them and FB either exciting or inhibiting them. These findings demonstrate that feedforward and feedback pathways serve distinct functional roles within recurrent cortical loops.